What is Mycobacterium Tuberculosis?

Mycobacterium tuberculosis (M. tuberculosis), a non-motile, obligately aerobic, intracellular bacterium known to cause Tuberculosis (TB), was discovered by Robert Koch in 1882 [1]. TB primarily affects the lungs along with the abdomen, bones, nervous system, reproductive system, liver, and lymph glands [2].

Pulmonary Tuberculosis ( TB ): Chest x-ray shows alveolar infiltration at both lungs due to Mycobacterium tuberculosis infection

Global Burden of the Disease

The World Health Organization (WHO) has reported a 22% decrease in TB-related mortality between 2000-2015, with a gradual 1.5% decrease in the annual rate. However, despite this trend and successful control of disease transmission, TB continues to have a significantly higher rate of morbidity. In 2015, six countries (China, India, Nigeria, Pakistan, Indonesia, and South Africa) accounted for 60% of TB-related deaths [3].

Global cases of Tuberculosis between 1965-2019

Pathogenicity of Mycobacterium Tuberculosis

Mycobacterium tuberculosis is transmitted in the form of droplet nuclei exhaled by individuals affected with laryngeal/pulmonary TB. It enters the body via the nasal cavity/mouth and travels to the alveoli of the lungs, where it recruits macrophages, in turn transporting the bacteria to the deeper tissues [4]. Another round of macrophage recruitment to the originally infected locus forms an organized aggregate of differentiated macrophages and immune cells called a granuloma. The infected granuloma undergoes necrosis, promoting bacterial growth and transmission to the next host [5].

Diagnosis of TB Infection

Some patients with TB may present with non-specific findings such as anemia, weight loss, fever of unknown origin, and fatigue; while others may be asymptomatic and show no abnormalities on physical examination [6]. Thus, the physician should collect body fluids/tissues for Acid-Fast bacilli (AFB) smear and culture.  Only a positive culture can confirm the diagnosis of TB. This is why TB tests are common practice in health care settings as is the prevention and disease control of tuberculosis. Testing for TB is critical to the prevention of the spread of the bacteria because knowing if you have an infection can be the first step in making sure that you are not spreading that same infection to those around you.

Confirmatory and diagnostic testing for TB:

• Culture, followed by Ziehl-Neelsen (AFB) staining
• A Chest X-ray to confirm the diagnosis in case of positive culture, indicating active disease
• Gene-based testing and nuclear amplification to identify the bacterial strains using DNA-based molecular techniques, such as GeneXpert [7].

Ziehl-Neelsen staining

AFB staining is the traditional method of TB diagnosis, as it is inexpensive and provides rapid results [8]. Mycobacterium species retain dyes when heated and treated with acidified organic compounds. The most common acid-fast staining method for M. tuberculosis is the Ziehl-Neelsen stain method, in which a bacteria specimen is fixed, stained with carbol-fuchsin dye, and decolorized with an acid-alcohol mixture. After counter-staining the smear with methylene blue or a similar dye, AFB appears red against a contrasting blue background [9].  In general, a sputum sample must contain at least 10,000 organisms/mL to visualize these bacteria at 100x magnification. 

Latent TB vs. Active TB

Latent TB represents the condition where the body’s immune system restricts the growth of M. tuberculosis bacterium, making the individual appear asymptomatic [10]. This can make tracking the prevention of spreading TB and disease control success difficult. Research has shown that its important for latent cases to be considered.

An individual with latent TB infection shows

• no symptoms.
• is not infectious (cannot spread TB).
• tests positive for TB blood/skin tests.
• may eventually develop active TB if the immune system weakens.

Active TB represents a condition where the body’s immune system is unable to restrict the growth of M. tuberculosis, rendering patients both ill and contagious. This is what most people think of when they think of a TB infection.

The symptoms of TB depend on the affected area.

a. General symptoms include:

• Night sweats
• Weight loss
• Prolonged fever
• Loss of appetite
• Fatigue

b. Symptoms of Pulmonary TB (infected lungs):

• Shortness of breath, which progressively worsens
• A persistent cough that produces phlegm and sometimes blood, persisting  > 3 weeks. 

c. Symptoms in the case when other areas of the body are infected:

• Swellings in the neck or other regions
• Pain in a joint or affected bone
• Abdominal pain
• Headache
• Confusion
• Seizures

Treatment

According to the World Health Organization (WHO), first-line treatment for TB may include combinations of five essential drugs: Rifampicin (R), Isoniazid (H), Pyrazinamide (Z), Ethambutol (E), and Streptomycin (S) [11].  Patients with TB undergo a standardized treatment for 6 to 9 months, including an initial two-month course of Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol, followed by another 4-month course of Isoniazid and Rifampicin [12].

For patients with Multi Drug-Resistant Tuberculosis (MDR-TB), directly-observed therapy (DOT) is used. In DOT, drugs are administered at least six days/week under the direct observation of the physician [13, 14]

BCG vaccine

Bacillus Calmette-Guerin (BCG), a vaccine for TB, was introduced in 1921 to control tuberculosis in humans. It is administered at birth, primarily in regions with a high disease burden, such as India, South Africa, and Pakistan [15]. Widespread immunization using the BCG vaccine has facilitated a reduction in TB cases globally [16].

Risk Factors

Five-to-ten percent of people with latent TB who do not receive appropriate treatment will eventually develop active TB infection [17]

Individuals at a higher risk of contracting TB and developing an infection include:

• Those who have traveled to or are living in a country with a high prevalence of TB. 
• Those living in crowded conditions
• Those who have been in close contact with a person infected with TB
• Children ages <= 5 years who have tested positive for a TB infection
• People who reside or work with persons at high risk for TB infection, such as those in hospitals, correctional facilities, homeless shelters, residential homes for HIV-infected individuals, and nursing homes

Additionally, immune dysfunction associated with diabetes mellitus, HIV infection, cancer chemotherapy, malnutrition, and advanced age is associated with an increased risk of contracting TB. 

Additional conditions associated with high risk for tuberculosis include silicosis, substance abuse, malignancy, organ transplantation, corticosteroid therapy, Crohn’s disease, and rheumatoid arthritis.

Tuberculosis and HIV

Co-infection by TB and HIV places a diagnostic and therapeutic burden on the health care system. HIV infection has been shown to increase the risk of reactivation of latent TB by 20-fold. [18].

The GIDEON Difference in Public Health

GIDEON is one of the most well-known and comprehensive global databases for infectious diseases. Data is refreshed daily, and the GIDEON API allows medical professionals and researchers access to a continuous stream of data. Whether your research involves quantifying data, learning about specific microbes, or testing out differential diagnosis tools– GIDEON has you covered with a program that has met standards for accessibility excellence. Check out some of our other content like Web-Based Analytics for Investigation of Disease Outbreaks, Cellphones Are ‘Trojan Horses’ for Viruses, Study Finds, Globalization and Health, and If You Gotta Go, Are Public Restrooms Safe On A Road Trip?

References

1.     K. R, Die Aetiologie der Tuberculose [The aetiology of Tuberculosis.], Berlin: Berliner Klinische Wochenschrift, 1882.
2. F. K. Dye C, Disease Control Priorities in Developing Countries, New York:: Oxford University Press, 2006.
3. Z. J. B. Q. H. H. B. L. Y. J. L. Q. L. J. Pan Z, “The Gap Between Global Tuberculosis Incidence and the First Milestone of the WHO End Tuberculosis Strategy: An Analysis Based on the Global Burden of Disease 2017 Database.,” 2020.
4. CDC, How TB Spreads, CDC, 2016.
5. G. M. J. Jr., “Microbial pathogenesis of Mycobacterium Tuberculosis: dawn of a discipline,” Cell, no. 104, pp. 477-485, 2001.
6. J. D. E, Mycobacterial diseases of the lung and bronchial tree: Clinical and laboratory aspects of Tuberculosis, Boston: Brown and Company, 1974.
7. [Online]. Available: https://www.ncbi.nlm.nih.gov/books/NBK441916/.
8. B. J. R. Elizabeth A. Talbot, Molecular Medical Microbiology, 2015.
9. R. l. Kradin, Diagnostic Pathology of Infectious Disease, 2018.
10. World Health Organization, Guidelines on the management of latent Tuberculosis infection, Geneva: WHO, 2015.
11. World Health Organization, Implementing the WHO Stop TB Strategy: A Handbook for National Tuberculosis Control Programmes.
12. Gideononline, “www.gideonoline.com,” Gideon, 2021. [Online]
13. A. F. Z. L. F. E. Terracciano E, [Tuberculosis: an ever-present disease but difficult to prevent], Ig Sanita, 2020.
14. M.-R. K. R. R. C. R. Chaulk CP, Eleven years of community-based directly observed therapy for Tuberculosis, JAMA, 1995.
15. “www.journals.plos.org,” [Online]
16. Z. a. Lancione, “Using data science to improve knowledge around a century-old vaccine,” The BCG Atlas, 2020.
17. CDC. [Online]
18. G. C. G. R. N. P. Getahun H, “HIV infection-associated tuberculosis: the epidemiology and the response,” Pubmed, 2010.